Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000708762 | SCV000822205 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000708762 | SCV002692732 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-30 | criteria provided, single submitter | clinical testing | The p.L45V variant (also known as c.133C>G), located in coding exon 1 of the STK11 gene, results from a C to G substitution at nucleotide position 133. The leucine at codon 45 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in 1/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003117510 | SCV003787146 | uncertain significance | Peutz-Jeghers syndrome | 2022-09-20 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 584567). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 45 of the STK11 protein (p.Leu45Val). |
| Baylor Genetics | RCV004569398 | SCV005052879 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2024-02-07 | criteria provided, single submitter | clinical testing |